Although it is now generally recognized that a properly functioning thymus gland is necessary for both the development and maintenance of cell-mediated immunity, the mechanisms by which these are accomplished are poorly characterized. The impetus for the proposed study is based upon the recent purification to homogeneity, of thymosin, a thymic hormone which was isolated and purified in our laboratory from calf thymus tissue. A second impetus is the demonstration that this humoral factor circulates in the blood and can partially replace thymic function in neonatally thymectomized mice. The proposed research has the following objectives: 1) to elucidate the endocrine role of the thymus gland in relation to aging process in the lymphoid system, including both the ontogenesis and senescence of the immune response; 2) to determine the role of thymosin and an anti-thymosin serum in the etiology of diseases characterized by hyper- or hypo-thymic function; and 3) to characterize completely the structure(s) and mechanism of action of bovine and human thymosin. Experimental approaches will include 1) development and clinical application of a radioimmunoassay for human thymosin; 2) evaluation of thymosin-treated lymphocyte populations from normal, aged, or immunosuppressed mice as well as mice with autoimmune diseases, leukemia, and virus-induced neoplasms; 3) determination of the amino acid sequence of bovine and human thymosin; and 4) localization, and characterization of the thymosin receptor.